吸入式组合粉末配方用于治疗潜伏性和多抗药性结核病:配方和体外鉴定
Basanth Babu Eedara1,2, Claire Fan1, Shubhra Sinha1,3
1School of Pharmacy, University of Otago, Dunedin 9054, New Zealand.
Pharmaceutics
|September 28, 2023
概括
新的吸入式干粉配方的普雷托曼尼德和皮拉津胺或莫西弗洛克萨辛为治疗结核病 (TB) 提供了一个有希望的策略,包括多抗药形式,通过将药物直接输送到肺部.
科学领域:
- 制药科学 制药科学
- 传染性疾病 传染性疾病
- 药物运输 药物运输 药物运输
背景情况:
- 结核病 (TB) 仍然是全球卫生危机,每年有数百万人死亡,并由潜伏感染和多药耐药菌株复杂化.
- 通过干粉吸入器 (DPI) 进行吸入药物输送,在结核病治疗中比口服药物更有优势,包括直接肺部输送和减少全身副作用.
- 普雷托曼尼德 (PA-824,PA) 是一种新型抗结核药物,对活跃和潜伏的Mycobacterium tuberculosis (Mtb) 有强烈的活性,与pyrazinamide (PYR) 和moxifloxacin (MOX) 具有协同效应.
研究的目的:
- 开发PYR和PA,或PYR和MOX的固定剂量组合干粉配方,用于吸入,以准MTB肺息地.
- 描述这些新型DPI配方的物理化学特性和体外气溶性能.
- 为了评估储存后组合药物粉末的稳定性.
主要方法:
- 固定剂量组合粉末 (PYR-PA和PYR-MOX) 用喷雾干燥与L-素作为气溶增强剂进行制备.
- 配方的特征是粒子大小,形态和固态特性.
- 试验室气溶剂使用下一代冲击器进行了评估,在受控的储存条件下评估了稳定性.
主要成果:
- 使用L-氨酸喷雾干燥产生球形,孔的颗粒 (PYR-PA为1.9微米,PYR-MOX为2.4微米).
- 粉末配方表现出高的气溶效率,排放剂量超过83%,细颗粒分数超过65%.
- 与pyrazinamide相比,pretomanid和moxifloxacin在组合粉末中表现出更好的稳定性.
结论:
- 成功开发了PYR-PA和PYR-MOX的新型固剂组合干粉吸入器配方.
- 这些配方具有出色的气溶性质,可以有效地输送到深肺.
- 开发的DPI代表了治疗潜伏性和多药耐药结核病感染的有希望的进展.
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